The preparation of brominated derivatives of guaiacol, more particularly 6-bromoguaiacol and 4-bromoguaiacol, is described in the literature.
EP 0338898 discloses preparation of 6-bromoguaiacol by bromination of guaiacol in isopropyl ether, using a solution of N,N-dibromo-tert-butylamine in isopropyl ether. The yield obtained is 75%.
According to Thomas Oberhauser (J. Org. Chem. 1997, 62, 4504-4506), guaiacol can be brominated in position 4 using NBS/HBF in acetonitrile. The yield obtained after 7 hours is 72%.
Hence the preparation of brominated derivatives of guaiacol in ortho or para position proves to be relatively easy.
In contrast, the preparation of the derivative 5-bromoguaiacol is much more difficult because the presence of electron-donating hydroxyl and methoxy groups promotes electrophilic substitutions in positions 6 and 4 and therefore leads more readily to the ortho- and para-bromophenol derivatives.